The present invention relates to new cephalosporin type compounds which have antimicrobial activities, and to a process for preparation thereof. More particularly, it relates to new cephem derivatives shown by the following formula(I) and pharmaceutically acceptable salts thereof or metabolically labile esters thereof, and to a process for preparing them. This invention also relates to pharmaceutical compositions comprising the new cephem compounds of the formula(I) as active ingredients ##STR2## wherein R.sup.1 is a hydrogen atom or an amino protecting group;
R.sup.2 is acetoxy, a heterocyclic group, or a sulfur atom linked with a heterocyclic group; and PA0 R.sup.3 is a hydrogen atom or a carboxyl protecting group (wherein when R.sup.2 contains quaternary ammonium, R.sup.2 and R.sup.3 may form a zwitter ion). PA0 R.sup.2 is acetoxy, a heterocyclic group, or a sulfur atom linked with a heterocyclic group; and PA0 R.sup.3 is a hydrogen atom or a carboxyl protecting group (wherein when R.sup.2 contains quaternary ammonium, R.sup.2 and R.sup.3 may form a zwitter ion).
Since the first discovery that cephalosporin derivatives exhibit potent antibiotic activities, a large number of cephalosporin type compounds possessing improved or broad antibiotic activities and high selectivity have been developed (Note, for example, J. Med. Chem. 12, 310(1969); U.S. Pat. No. 3,970,651, etc.). Nowadays, cephalosporin antibiotics are widely used in the treatment of diseases caused by pathogenic bacteria in human beings and animals, and are especially useful in the treatment of diseases caused by bacteria which are resistant to other antibiotics such as penicillin compounds and in the treatment of penicillin sensitive patients. In many instances, it is desirable to employ a cephalosporin antibiotic which exhibits activities against gram-positive and gram-negative bacteria, particularly Pseudomonas.
A number of cephalosporin compounds belonging to a class of 3-substituted or unsubstituted-3-cephem-4-carboxylic acids which contain 2-(2-aminothiazole-4-yl)-2-(substituted or unsubstituted alkoxyimino) acetamido group as shown in the following formula(A) at the 7-position of the cephalsporin nucleus have been known. ##STR3##
These antibiotic compounds are characterized by their high antibacterial activities against a range of gram-positive and gram-negative bacteria and particularly high stability of .beta.-lactamase produced by various gram-negative bacteria. Among such cephalosporin compounds, Cefotaxime of the formula(B) (U.S. Pat. No. 4,098,888) and Ceftazidime of the formula(C) (U.S. Pat. No. 4,258,041) are considerably effective in the treatment of diseases caused by general pathogenic bacteria. ##STR4##
In GB patent No. 1,399,086, many cephalosporin derivatives which are shown by the formula(D) are described. ##STR5## wherein R is a hydrogen atom or an organic group; R.sup.a is a primary alkyl group to form an ether linkage; B is -S- or ##STR6## and P is an organic group.
In U.S. Pat. No. 4,278,793, cephalosporin derivatives of the formula (E) are also described, ##STR7## wherein R.sup.1 is a hydrogen atom or an amino protecting group; R.sup.b is a hydrogen atom, an aliphatic group, acyl, aryl, alkoxy, arylsulfonyl or hetero aryl group; X is -S-, -O-, ##STR8## and A is an alkoxy, alkenyloxy group or a halogen atom.
In this way, the cephalosporin derivatives which have 2-(2-aminothiazol-4-yl)-2-(2-furfuryl-oxyimino)-acetamido group at 7-position are first mentioned in the present invention. The cephalsporin are first mentioned in the present invention. The cephalsporin compound of the formula(F) (RN=99951-28-7) which has 2-[2-triphenylmethyl)aminothiazol-4-yl]-2-(2-furanylcarbonyloxy imino)-acetamido group at 7-position is also a known compound, but this compound has no correlation with the present invention. ##STR9##